Reduced efficacy of a Src kinase inhibitor in crowded protein solution
نویسندگان
چکیده
Abstract The inside of a cell is highly crowded with proteins and other biomolecules. How express their specific functions together many off-target in cellular environments largely unknown. Here, we investigate an inhibitor binding c-Src kinase using atomistic molecular dynamics (MD) simulations dilute as well protein solution. populations the inhibitor, 4-amino-5-(4-methylphenyl)?7-( t -butyl)pyrazolo[3,4-d]pyrimidine (PP1), bulk solution on surface are reduced concentration crowder bovine serum albumins (BSAs) increases. This observation consistent PP1 efficacy experimental assays addition BSAs. environment changes major pathway toward compared to that change explained based population shift mechanism local conformations near site kinase.
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ژورنال
عنوان ژورنال: Nature Communications
سال: 2021
ISSN: ['2041-1723']
DOI: https://doi.org/10.1038/s41467-021-24349-5